Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane-bound TNF in experimental cerebral malaria
| Autor: | C. Giroud, T. de Kesel, M. Redard, Wim A. Buurman, P Juillard, E. Decoster, Danielle Burger, Rudolf Lucas, Horst Bluethmann, C. Monso-Hinard, Yves Donati, Mark W. Moore, Jean-Michel Dayer, Walter Fiers, Georges E. Grau |
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| Přispěvatelé: | Algemene Heelkunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty Endothelium Plasmodium berghei Immunology Malaria Cerebral Biology Receptors Tumor Necrosis Factor Pathogenesis Interferon-gamma Mice Antigens CD Internal medicine medicine Animals Receptors Tumor Necrosis Factor Type II Immunology and Allergy Receptor Mice Knockout Mice Inbred BALB C Tumor Necrosis Factor-alpha Microcirculation Cell Membrane Brain Intercellular Adhesion Molecule-1 Immunity Innate In vitro Up-Regulation Mice Inbred C57BL Endocrinology medicine.anatomical_structure Solubility Receptors Tumor Necrosis Factor Type I Cerebral Malaria Knockout mouse Mice Inbred CBA Tumor necrosis factor alpha Endothelium Vascular Intracellular |
| Zdroj: | European Journal of Immunology, 27(7), 1719-1725. Wiley |
| ISSN: | 0014-2980 |
| DOI: | 10.1002/eji.1830270719 |
| Popis: | Department of Anesthesiology, Pharmacology and Surgical Intensive Care, University Medical Center, Geneva, Switzerland.Tumor necrosis factor (TNF) has been implicated in the pathogenesis of experimental cerebral malaria (CM), but the respective role of its two types of receptors has not been established. A significant increase in the expression of TNF-receptor 2 (TNFR2, p75), but not of TNFR1 (p55), was found on brain microvessels at the time of CM in susceptible animals. Moreover, mice genetically deficient for TNFR2 (Tnfr2null) were significantly protected from experimental CM, in contrast to TNFR1-deficient (Tnfr1null) mice, which were as susceptible as wild-type mice. To identify the factors involved in the protection from CM conferred by the lack of TNFR2, we assessed in both knockout and control mice the serum concentrations of mediators that are critical for the development of CM, as well as the up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the brain microvessels. No significant difference in serum levels of TNF and interferon-gamma was found between infected wild-type and Tnfr1null or Tnfr2null mice. Interestingly, the pronounced ICAM-1 up-regulation and leukocyte sequestration, typically occurring in brain microvessels of CM-susceptible animals, was detected in infected control and Tnfr1null mice-both of which developed CM-whereas no such ICAM-1 up-regulation or leukocyte sequestration was observed in Tnfr2null mice, which were protected from CM. Making use of microvascular endothelium cells (MVEC) isolated from wild-type, Tnfr1null or Tnfr2null mice, we show that soluble TNF requires the presence of both TNF receptors, whereas membrane-bound TNF only needs TNFR2 for TNF-mediated ICAM-1 up-regulation in brain MVEC. Thus, only in MVEC lacking TNFR2, neither membrane-bound nor soluble TNF cause the up-regulation of ICAM-1 in vitro. In conclusion, these results indicate that the interaction between membrane TNF and TNFR2 is crucial in the development of this neurological syndrome. |
| Databáze: | OpenAIRE |
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